Buccal, polar and non-polar spray or capsule containing drugs for treating pain

ABSTRACT

Buccal aerosol sprays or capsules using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprise formulation I: aqueous polar solvent, active compound, and optional flavoring agent; formulation II: aqueous polar solvent, active compound, optionally flavoring agent, and propellant; formulation m: non-polar solvent, active compound, and optional flavoring agent; and formulation IV: non-polar solvent, active compound, optional flavoring agent, and propellant.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of application Ser. No. 09/537,118, filed Mar. 29, 2000 which is a continuation-in-part of the U.S. national phase designation of PCT/US97/17899 filed Oct. 1, 1997, the disclosures of which are incorporated by reference herein in their entirety.

BACKGROUND OF THE INVENTION

[0002] It is known that certain biologically active compounds are better absorbed through the oral mucosa than through other routes of administration, such as through the stomach or intestine. However, formulations suitable for such administration by these latter routes present their own problems. For example, the biologically active compound must be compatible with the other components of the composition such as propellants, solvents, etc. Many such formulations have been proposed. For example, U.S. Pat. No. 4,689,233, Dvorsky et al., describes a soft gelatin capsule for the administration of the anti-coronary drug nifedipine dissolved in a mixture of polyether alcohols. U.S. Pat. No. 4,755,389, Jones et al., describes a hard gelatin chewable capsule containing nifedipine. A chewable gelatin capsule containing a solution or dispersion of a drug is described in U.S. Pat. No. 4,935,243, Borkan et al. U.S. Pat. No. 4,919,919, Aouda et al, and U.S. Pat. No. 5,370,862, Klokkers-Bethke, describe a nitroglycerin spray for administration to the oral mucosa comprising nitroglycerin, ethanol, and other components. An orally administered pump spray is described by Cholcha in U.S. Pat. No. 5,186,925. Aerosol compositions containing a hydrocarbon propellant and a drug for administration to a mucosal surface are described in U.K. 2,082,457, Su, U.S. Pat. No. 3,155,574, Silson et al., U.S. Pat. No. 5,011,678, Wang et al., and by Parnell in U.S. Pat. No. 5,128,132. It should be noted that these references discuss bioavailability of solutions by inhalation rather than through the membranes to which they are administered.

SUMMARY OF THE INVENTION

[0003] A buccal aerosol spray or soft bite gelatin capsule using a polar or non-polar solvent has now been developed which provides biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect.

[0004] The buccal aerosol spray compositions of the present invention, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable non-polar solvent comprise in weight % of total composition: pharmaceutically acceptable propellant 5-80%, nonpolar solvent 19-85%, active compound 0.05-50%, suitably additionally comprising, by weight of total composition a flavoring agent 0.01-10%. Preferably the composition comprises: propellant 10-70%, non-polar solvent 25-89.9%, active compound 0.01-40%, flavoring agent 1-8%; most suitably propellant 20-70%, non-polar solvent 25-74.75%, active compound 0.25-35%, flavoring agent 2-7.5%.

[0005] The buccal polar aerosol spray compositions of the present invention, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent are also administrable in aerosol form driven by a propellant. In this case, the composition comprises in weight % of total composition: aqueous polar solvent 10-97%, active compound 0.1-25%, suitably additionally comprising, by weight of total composition a flavoring agent 0.05-10% and propellant: 2-10%. Preferably the composition comprises: polar solvent 20-97%, active compound 0.1-15%, flavoring agent 0.1-5% and propellant 2-5%; most suitably polar solvent 25-97%, active compound 0.2-25%, flavoring agent 0.1-2.5% and propellant 2-4%.

[0006] The buccal pump spray composition of the present invention, i.e., the propellant free composition, for transmucosal administration of a pharmacologically active compound wherein said active compound is soluble in a pharmacologically acceptable non-polar solvent comprises in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55%, and suitably additionally, flavoring agent 0.1-10%.

[0007] The buccal polar pump spray compositions of the present invention, i.e., the propellant free composition, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent comprises in weight % of total composition: aqueous polar solvent 30-99.69%, active compound 0.001-60%, suitably additionally comprising, by weight of total composition a flavoring agent 0.1-10%. Preferably the composition comprises: polar solvent 37-98.58%, active compound 0.005-55%, flavoring agent 0.5-8%; most suitably polar solvent 60.9-97.06%, active compound 0.01-40%, flavoring agent 0.75-7.5%.

[0008] The soft bite gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable non-polar solvent, having charged thereto a fill composition comprise in weight % of total composition: non-polar solvent 4-99.99%, emulsifier 0-20%, active compound 0.01-80%, provided that said fill composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 0.01-10%. Preferably, the soft bite gelatin capsule comprises: non-polar solvent 21.5-99.975%, emulsifier 0-15%, active compound 0.025-70%, flavoring agent 1-8%; most suitably: nonpolar solvent 28.5-97.9%, emulsifier 0-10%, active compound 0.1-65.0%, flavoring agent 2-6%.

[0009] The soft bite polar gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable polar solvent, having charged thereto a composition comprising in weight % of total composition: polar solvent 25-99.89%, emulsifier 0-20%, active compound 0.01-65%, provided that said composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 01-10%. Preferably, the soft bite gelatin capsule comprises: polar solvent 37-99.95%, emulsifier 0-15%, active compound 0.025-55%, flavoring agent 1-8%; most suitably: polar solvent 44-96.925%, emulsifier 0-10%, active compound 0.075-50%, flavoring agent 2-6%.

[0010] It is an object of the invention to coat the mucosal membranes either with extremely fine droplets of spray containing the active compounds or a solution or paste thereof from bite capsules.

[0011] It is also an object of the invention to administer to the oral mucosa of a mammalian in need of same, preferably man, by spray or bite capsule, a predetermined amount of a biologically active compound by this method or from a soft gelatin capsule.

[0012] A further object is a sealed aerosol spray container containing a composition of the non polar or polar aerosol spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.

[0013] As the propellant evaporates after activation of the aerosol valve, a mist of fine droplets is formed which contains solvent and active compound.

[0014] The propellant is a non-Freon material, preferably a C₃₋₈ hydrocarbon of a linear or branched configuration. The propellant should be substantially non-aqueous. The propellant produces a pressure in the aerosol container such that under expected normal usage it will produce sufficient pressure to expel the solvent from the container when the valve is activated but not excessive pressure such as to damage the container or valve seals.

[0015] The non-polar solvent is a non-polar hydrocarbon, preferably a C₇₋₁₈ hydrocarbon of a linear or branched configuration, fatty acid esters, and triglycerides, such as miglyol. The solvent must dissolve the active compound and be miscible with the propellant, i.e., solvent and propellant must form a single phase at a temperature of 0-40° C. a pressure range of between 1-3 atm.

[0016] The polar and non-polar aerosol spray compositions of the invention are intended to be administered from a sealed, pressurized container. Unlike a pump spray, which allows the entry of air into the container after every activation, the aerosol container of the invention is sealed at the time of manufacture. The contents of the container are released by activation of a metered valve, which does not allow entry of atmospheric gasses with each activation. Such containers are commercially available.

[0017] A further object is a pump spray container containing a composition of the pump spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.

[0018] A further object is a soft gelatin bite capsule containing a composition of as set forth above. The formulation may be in the form of a viscous solution or paste containing the active compounds. Although solutions are preferred, paste fills may also be used where the active compound is not soluble or only partially soluble in the solvent of choice. Where water is used to form part of the paste composition, it should not exceed 10% thereof. (All percentages herein are by weight unless otherwise indicated.)

[0019] The polar or non-polar solvent is chosen such that it is compatible with the gelatin shell and the active compound. The solvent preferably dissolves the active compound. However, other components wherein the active compound is not soluble or only slightly soluble may be used and will form a paste fill.

[0020] Soft gelatin capsules are well known in the art. See, for example, U.S. Pat. No. 4,935,243, Borkan et al., for its teaching of such capsules. The capsules of the present invention are intended to be bitten into to release the low viscosity solution or paste therein, which will then coat the buccal mucosa with the active compounds. Typical capsules, which are swallowed whole or bitten and then swallowed, deliver the active compounds to the stomach, which results in significant lag time before maximum blood levels can be achieved or subject the compound to a large first pass effect. Because of the enhanced absorption of the compounds through the oral mucosa and no chance of a first pass effect, use of the bite capsules of the invention will eliminate much of the lag time, resulting in hastened onset of biological effect. The shell of a soft gelatin capsule of the invention may comprise, for example: gelatin: 50-75%, glycerin 20-30%, colorants 0.5-1.5%, water 5-10%, and sorbitol 2-10%.

[0021] The active compound may include, biologically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostaglandins and neutraceuticals.

[0022] The active compounds may also include antihistamines, alkaloids, hormones, benzodiazepines and narcotic analgesics. While not limited thereto, these active compounds are particularly suitable for non-polar pump spray formulation and application.

[0023] The active compounds may also include nerve impulse inhibitors, anti-opioid agents, anti-migraine agents, anti-muscle spasm agents, pain control agents, anesthetics, anti-inflammatory drugs, or mixtures thereof.

BRIEF DESCRIPTION OF THE DRAWING

[0024]FIG. 1. is a schematic diagram showing routes of absorption and processing of pharmacologically active substances in a mammalian system.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] The preferred active compounds of the present invention are in an ionized, salt form or as the free base of the pharmaceutically acceptable salts thereof (provided, for the aerosol or pump spray compositions, they are soluble in the spray solvent). These compounds are soluble in the non-polar solvents of the invention at useful concentrations or can be prepared as pastes at useful concentrations. These concentrations may be less than the standard accepted dose for these compounds since there is enhanced absorption of the compounds through the oral mucosa. This aspect of the invention is especially important when there is a large (40-99.99%) first pass effect.

[0026] As propellants for the non polar sprays, propane, N-butane, iso-butane, N-pentane, iso-pentane, and neo-pentane, and mixtures thereof may be used. N-butane and iso-butane, as single gases, are the preferred propellants. It is permissible for the propellant to have a water content of no more than 0.2%, typically 0.1-0.2%. All percentages herein are by weight unless otherwise indicated. It is also preferable that the propellant be synthetically produced to minimize the presence of contaminants which are harmful to the active compounds. These contaminants include oxidizing agents, reducing agents, Lewis acids or bases, and water. The concentration of each of these should be less than 0.1%, except that water may be as high as 0.2%.

[0027] Suitable non-polar solvents for the capsules and the non-polar sprays include (C₂-C₂₄) fatty acid (C₂-C₆) esters, C₇-C₁₈ hydrocarbon, C₂-C₆ alkanoyl esters, and the triglycerides of the corresponding acids. When the capsule fill is a paste, other liquid components may be used instead of the above low molecular weight solvents. These include soya oil, corn oil, other vegetable oils.

[0028] As solvents for the polar capsules or sprays there may be used low molecular weight polyethyleneglycols (PEG) of 400-1000 Mw (preferably 400-600), low molecular weight (C₂-C₈) mono and polyols and alcohols of C₇-C₁₈ linear or branch chain hydrocarbons, glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.

[0029] It is expected that some glycerin and water used to make the gelatin shell will migrate from the shell to the fill during the curing of the shell. Likewise, there may be some migration of components from the fill to the shell during curing and even throughout the shelf-life of the capsule.

[0030] Therefore, the values given herein are for the compositions as prepared, it being within the scope of the invention that minor variations will occur.

[0031] The preferred flavoring agents are synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners (sugars, aspartame, saccharin, etc.), and combinations thereof.

[0032] The active substances include the active compounds selected from the group consisting of cyclosporine, sermorelin, octreotide acetate, calcitonin-salmon, insulin lispro, sumatriptan succinate, clozepine, cyclobenzaprine, dexfenfluramine hydrochloride, glyburide, zidovudine, erythromycin, ciprofloxacin, ondansetron hydrochloride, dimenhydrinate, cimetidine hydrochloride, famotidine, phenytoin sodium, phenytoin, carboprost thromethamine, carboprost, diphenhydramine hydrochloride, isoproterenol hydrochloride, terbutaline sulfate, terbutaline, theophylline, albuterol sulfate and neutraceuticals, that is to say nutrients with pharmacological action such as but not limited to camitine, valerian, echinacea, and the like.

[0033] In another embodiment, the active compound is a nerve impulse inhibitor, anti-opioid agent, anti-migraine agent, anti-muscle spasm agent, pain control agent, anesthetic, anti-inflammatory drug, or a mixture thereof.

[0034] In one embodiment the active compound is a nerve impulse inhibitor. Suitable nerve impulse inhibitors for use in the buccal sprays of the invention include, but are not limited to levobupivacaine, lidocaine, prilocalne, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxacurium, mivacurium, pancuronium, vecuronium, pipecuronium, rocuronium, and mixtures thereof.

[0035] In one embodiment the active compound is an anti-opioid agent. Suitable anti-opioid agents for use in the buccal sprays of the invention include, but are not limited to, naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.

[0036] In one embodiment the active compound is an anti-migraine agent. Suitable anti-migraine agents for use in the buccal sprays of the invention include, but are not limited to, frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.

[0037] In one embodiment the active compound is an anti-muscle spasm agent. Suitable anti-muscle spasm agents for use in the buccal sprays of the invention include, but are not limited to, baclofen, botulinum toxin, carisoprodol, chlorphenesin, chlorzoxazone, cyclobenzaprine, dantrolene, diazepam, metaxalone, methocarbamol, orphenadrine, tizanidine, and mixtures thereof.

[0038] In one embodiment the active compound is a pain control agent. Suitable pain control agents for use in the buccal sprays of the invention include, but are not limited to, non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.

[0039] In one embodiment the active compound is an anesthetic. Suitable anesthetics for use in the buccal sprays of the invention include, but are not limited to, benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.

[0040] In one embodiment the active compound is an anti-inflammatory drug. Suitable anti-inflammatory drugs for use in the buccal sprays of the invention include, but are not limited to, alosetron, anakinra, beclomethasone, betamethasone, budesonide, clobetasol, celecoxib, cromolyn, desoximetasone, dexamethasone, epinastic, etanercept, etoricoxib, flunisolide, fluocinonide, fluticasone, formoterol, hydrocortisone, hydroxychloroquine, ibudilast, ketotifen, meloxicam, mesalamine, methotrexate, methylprednisolone, mometasone, montelukast, nedocromil, olsalazine, prednisone, ramatroban, rofecoxib, salsalate, terbutaline, triamcinolone, valdecoxib, zafirlukast, and mixtures thereof.

[0041] The formulations of the present invention comprise an active compound or a pharmaceutically acceptable salt thereof. The term “pharmaceutically acceptable salts” refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases including organic and inorganic acids or bases.

[0042] When an active compound of the present invention is acidic, salts may be prepared from pharmaceutically acceptable non-toxic bases. Salts derived from all stable forms of inorganic bases include aluminum, ammonium, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium, zinc, etc. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion-exchange resins such as arginine, betaine, caffeine, choline, N,N dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethyl-aminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, isopropylamine, lysine, methyl-glucosamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, etc.

[0043] When an active compound of the present invention is basic, salts may be prepared from pharmaceutically acceptable non-toxic acids. Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethane-sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, etc. Particularly preferred are citric, hydrobromic, maleic, phosphoric, sulfuric, and tartaric acids.

[0044] In the discussion of methods of treatment herein, reference to the active compounds is meant to also include the pharmaceutically acceptable salts thereof. While certain formulations are set forth herein, the actual amounts to be administered to the mammal or man in need of same are to be determined by the treating physician.

[0045] The invention is further defined by reference to the following examples, which are intended to be illustrative and not limiting.

[0046] The following are examples of certain classes. All values unless otherwise specified are in weight percent.

EXAMPLES

[0047] Example 1

Biologically Active Peptides Including Peptide Hormones

[0048] A. Cyclosporine lingual spray most Amounts preferred amount preferred amount cyclosporine 5-50 10-35 15-25 water 5-20 7.5-50  9.5-12  ethanol 5-60 7.5-50  10-20 polyethylene glycol 20-60  30-45 35-40 flavors 0.1-5   1-4 2-3

[0049] B. Cyclosporine Non-Polar lingual spray preferred most Amounts amount preferred amount cyclosporine  1-50  3-40  5-30 Migylol 20 25 30-40 Polyoxyethylated castor oil 20 25 30-40 Butane 25-80 30-70 33-50 flavors 0.1-5   1-4 2-3

[0050] C. Cyclosporine non-polar bite caosule Amounts preferred amount most preferred amount cyclosporine  1-35  5-25 10-20 olive oil 25-60 35-55 30-45 polyoxyethylated 25-60 35-55 30-45 oleic glycerides flavors 0.1-5   1-4 2-3

[0051] D. Cyclosporine bite capsule most Amounts preferred amount preferred amount cyclosporine 5-50 10-35 15-25 polyethylene glycol 20-60  30-45 35-40 glycerin 5-30 7.5-25  10-20 propylene glycol 5-30 7.5-25  10-20 flavors 0.1-10   1-8 3-6

[0052] E. Sermorelin (as the acetate) lingual spray preferred Amounts amount most preferred sermorelin (as the acetate) .01-5   .1-3   .2-1.0 mannitol  1-25  5-20 10-15 monobasic sodium phosphate, 0.1-5    1-31  .5-2.5 dibasic sodium phosphate water 0.01-5   .05-3   0.1-0.5 ethanol  5-30 7.5-25  9.5-15  polyethylene glycol 20-60 30-45 35-40 propylene glycol  5-25 10-20 12-17 flavors 0.1-5   1-4 2-3

[0053] F. Octreotide acetate (Sandostatin) lingual spray most Amounts preferred amount preferred amount octreotide acetate 0.001-0.5  0.005-0.250 0.01-0.10 acetic acid  1-10 2-8 4-6 sodium acetate  1-10 2-8 4-6 sodium chloride  3-30  .5-25  15-20 flavors 0.1-5   0.5-.4  2-3 ethanol  5-30 7.5-20  9.5-15  water 15-95 35-90 65-85 flavors 0.1-5   1-4 2-3

[0054] G. Calcitonin-salmon lingual spray most Amounts preferred amount preferred amount calcitonin-salmon 0.001-5    0.005-2     01-1.5 ethanol  2-15  3-10   7-9.5 water 30-95 50-90 60-80 polyethylene glycol  2-15  3-10   7-9.5 sodium chloride 2.5-20   5-15   10-12.5 flavors 0.1-5   1-4 2-3

[0055] H. Insulin lispro, lingual spray most preferred Amounts preferred amount amount insulin 20-60  4-55  5-50 glycerin 0.1-10  0.25-5   0.1-1.5 dibasic sodium  1-15 2.5-10  4-8 phosphate m-cresol,  1-25  5-25  7.5-12.5 zinc oxide 0.01-0.25  .05-0.15 0.075-0.10  m-cresol 0.1-1   0.2-0.8 0.4-0.6 phenol trace amounts trace amounts trace amounts ethanol  5-20 7.5-15   9-12 water 30-90 40-80 50-75 propylene glycol  5-20 7.5-15   9-12 flavors 0.1-5   0.5-3   0.75-2  

Example 2

[0056] CNS active amines and their salts: including but not limited to tricyclic amines, GABA analogues, thiazides, phenothiazine derivatives, serotonin antagonists and serotonin reuptake inhibitors A. Sumatriptan succinate lingual spray most Amounts preferred amount preferred amount sumatriptan succinate 0.5-30    1-20 10-15 ethanol 5-60 7.5-50  10-20 propylene glycol 5-30 7.5-20  10-15 polyethylene glycol 0-60 30-45 35-40 water 5-30 7.5-20  10-15 flavors 0.1-5   1-4 2-3

[0057] B. Sumatriptan succinate bite capsule most Amounts preferred amount preferred amount sumatriptan succinate 0.01-5   0.05-3.5  0.075-1.75  polyethylene glycol 25-70 30-60 35-50 glycerin 25-70 30-60 35-50 flavors 0.1-10  1-8 3-6

[0058] C. Clozepine lingual spray most Amounts preferred amount preferred amount clozepine 0.5-30     1-20 10-15 ethanol 5-60 7.5-50 10-20 propylene glycol 5-30 7.5-20 10-15 polyethylene glycol 0-60  30-45 35-40 water 5-30 7.5-20 10-15 flavors 0.1-5    1-4 2-3

[0059] D. Clozepine non-polar lingual spray with propellant Amounts preferred amount most preferred amount clozepine 0.5-30  1-20 10-15 Migylol  20-85 25-70 30-40 Butanol   5-80 30-75 60-70 flavors 0.1-5 1-4 2-3

[0060] E. Clozepine non-polar lingual spray without propellant Amounts preferred amount most preferred amount clozepine 0.5-30   1-20 10-15 Migylol   70-99.5 80-99 85-90 flavors 0.1-5   1-4 2-3

[0061] F. Cyclobenzaprine non-polar lingual spray Amounts preferred amount most preferred amount cyclobenzaprine 0.5-30   1-20 10-15 (base) Migylol 20-85 25-70 30-40 Iso-butane 15-80 30-75 60-70 flavors 0.1-5   1-4 2-3

[0062] G. Dexfenfluramine hydrochloride lingual spray most Amounts preferred amount preferred amount dexfenfluramine Hcl 5-30 7.5-20 10-15 ethanol 5-60 7.5-50 10-20 propylene glycol 5-30 7.5-20 10-15 polyethylene glycol 0-60  30-45 35-40 water 5-30 7.5-20 10-15 flavors 0.1-5    1-4 2-3

Example 3 Sulfonylureas

[0063] A. Glyburide lingual spray most Amounts preferred amount preferred amount glyburide 0.25-25   0.5-20  0.75-15   ethanol  5-60 −7.5-50   10-20 propylene glycol  5-30 7.5-20  10-15 polyethylene glycol  0-60 30-45 35-40 water 2.5-30   5-20  6-15 flavors 0.1-5   1-4 2-3

[0064] B. Glyburide non-polar bite capsule most Amounts preferred amount preferred amount glyburide 0.01-10   0.025-7.5  0.1-4   olive oil 30-60 35-55 30-50 polyoxyethylated oleic 30-60 35-55 30-50 glycerides flavors 0.1-5   1-4 2-3

Example 4 Antibiotics Anti-Fungals and Anti-Virals

[0065] A. Zidovudine [formerly called azidothymidine (AZT) (Retrovir)] non-polar lingual spray Amounts preferred amount most preferred amount zidovudine 10-50 15-40 25-35 Soya oil 20-85 25-70 30-40 Butane 15-80 30-75 60-70 flavors 0.1-5   1-4 2-3

[0066] B. Erythromycin bite capsule bite capsule most preferred Amounts preferred amount amount erythromycin 25-65  30-50 35-45 polyoxyethylene glycol 5-70 30-60 45-55 glycerin 5-20 7.5-15    10-12.5 flavors 1-10 2-8 3-6

[0067] C. Ciprofloxacin hydrochloride bite capsule preferred most preferred Amounts amount amount ciprofloxacin hydrochloride 25-65  35-55 40-50 glycerin 5-20 7.5-15    10-12.5 polyethylene glycol 120-75  30-65 40-60 flavors 1-10 2-8 3-6

[0068] D. zidovudine [formerly called azidothymidine (AZT) (Retrovir)] lingual spray most preferred Amounts preferred amount amount zidovudine 10-50 15-40 25-35 water 30-80 40-75 45-70 ethanol  5-20 7.5-15   9.5-12.5 polyethylene glycol  5-20 7.5-15   9.5-12.5 flavors 0.1-5   1-4 2-3

Example 5

[0069] Anti-Emetics A. Ondansetron hydrochloride lingual spray preferred most preferred Amounts amount amount ondansetron hydrochloride 1-25  2-20 2.5-15 citric acid monohydrate 1-10 2-8 2.5-5  sodium citrate dihydrate 0.5-5   1-4 1.25-2.5  water 1-90  5-85  10-75 ethanol 5-30 7.5-20  9.5-15 propylene glycol 5-30 7.5-20  9.5-15 polyethylene glycol 5-30 7.5-20  9.5-15 flavors 1-10 3-8  5-7.5

[0070] B. Dimenhydrinate bite capsule most Amounts preferred amount preferred amount dimenhydrinate 0.5-30   2-25  3-15 glycerin  5-20 7.5-15    10-12.5 polyethylene glycol 45-95 50-90 55-85 flavors  1-10 2-8 3-6

[0071] C. Dimenhydrinate polar lingual spray most Amounts preferred amount preferred amount dimenhydrinate 3-50 4-40 5-35 water 5-90 10-80  15-75  ethanol 1-80 3-50 5-10 polyethylene glycol 1-80 3-50 5-15 sorbitol 0.1-5   0.2-40   0.4-1.0  aspartame 0.01-0.5  0.02-0.4  0.04-0.1  flavors 0.1-5   1-4  2-3 

Example 6

[0072] Histamine H-2 Receptor Antagonists A. Cimetidine hydrochloride bite capsule most Amounts preferred amount preferred amount cimetidine HCl 10-60 15-55 25-50 glycerin  5-20 7.5-15    10-12.5 polyethylene glycol 20-90 25-85 30-75 flavors  1-10 2-8 3-6

[0073] B. Famotidine lingual spray most Amounts preferred amount preferred amount famotidine  1-35 5-30 7-20 water 2.5-25  3-20 5-10 L-aspartic acid 0.1-20  1-15 5-10 polyethylene glycol 20-97 30-95  50-85  flavors 0.1-10   1-7.5 2-5 

[0074] C. Famotidine non-polar lingual spray Amounts preferred amount most preferred amount famotidine  1-35  5-30  7-20 Soya oil 10-50 15-40 15-20 Butane 1  5-80 30-75 45-70 polyoxyethylated 10-50 15-40 15-20 oleic glycerides flavors 0.1-5   1-4 2-3

Example 7 Barbiturates

[0075] A. Phenytoin sodium lingual spray most Amounts preferred amount preferred amount phenytoin sodium 10-60   15-55  20-40 water 2.5-25     3-20   5-10 ethanol 5-30 7.5-20 9.5-15 propylene glycol 5-30 7.5-20 9.5-15 polyethylene glycol 5-30 7.5-20 9.5-15 flavors 1-10  3-8  5-7.5

[0076] B. Phenytoin non-polar lingual spray most preferred Amounts preferred amount amount phenytoin  5-45 10-40 15-35 migylol 10-50 15-40 15-20 Butane 15-80 30-75 60-70 polyoxyethylated 10-50 15-40 15-20 oleic glycerides flavors 0.1-10  1-8   5-7.5

Example 8 Prostaglandins

[0077] A. Carboprost thromethamine lingual spray preferred most preferred Amounts amount amount carboprost thromethamine 0.05-5    0.1-3  0.25-2.5  water 50-95   60-80 65-75 ethanol 5-20 7.5-15  9.5-12.5 polyethylene glycol 5-20 7.5-15  9.5-12.5 sodium chloride 1-20   3-15 4-8 flavors 0.1-5     1-4 2-3

[0078] pH is adjusted with sodium hydroxide and/or hydrochloric acid B. Carboprost non-polar lingual spray Amounts preferred amount most preferred amount carboprost 0.05-5   0.1-3   0.25-2.5  migylol 25-50 30-45 35-40 Butane  5-60 10-50 20-35 polyoxyethylated 25-50 30-45 35-40 oleic glycerides flavors 0.1-10  1-8   5-7.5

Example 9 Neutraceuticals

[0079] A. Carnitine as bite capsule (contents are a paste) Amounts preferred amount most preferred amount carnitine  6-80 30-70 45-65 fumarate soya oil 7.5-50  10-40 12.5-35   soya lecithin 0.001-1.0  0.005-0.5  .01-0.1 Soya fats 7.5-50  10-40 12.5-35   flavors  1-10 2-8 3-6

[0080] B. Valerian as lingual spray Amounts preferred amount most preferred amount valerian extract 0.1-10  0.2-7   0.25-5   water 50-95 60-80 65-75 ethanol  5-20 7.5-15   9.5-12.5 polyethylene  5-20 7.5-15   9.5-12.5 glycol flavors  1-10 2-8 3-6

[0081] C. Echinacea as bite capsule Amounts preferred amount most preferred amount echinacea 30-85 40-75 45-55 extract soya oil 7.5-50  10-40 12.5-35   soya lecithin 0.001-1.0  0.005-0.5  .01-0.1 Soya fats 7.5-50  10-40 12.5-35   flavors  1-10 2-8 3-6

[0082] D. Mixtures of ingredients Amounts preferred amount most preferred amount magnesium oxide 15-40 20-35 25-30 chromium 0.01-1.0  0.02-0.5  .025-0.75 picolinate folic acid .025-3.0  0.05-2.0  0.25-0.5  vitamin B-12 0.01-1.0  0.02-0.5  .025-0.75 vitamin E 15-40 20-35 25-30 Soya oil 10-40 12.5-35   15-20 soya lecithin 0.1-5   0.2-4   0.5-1.5 soya fat 10-40 15-35 17.5-20  

Example 10 Sleep Inducers (Also CNS Active Amine)

[0083] A. Diphenhydramine hydrochloride lingual spray Amounts preferred amount most preferred amount diphenhydramine  3-50.  4-40  5-35 HCl water  5-90 10-80 50-75 ethanol  1-80  3-50  5-10 polyethylene  1-80  3-50  5-15 glycol Sorbitol 0.1-5   0.2-4   0.4-1.0 aspartame 0.01-0.5  0.02-0.4  0.04-0.1  flavors 0.1-5   1-4 2-3

Example 11 Anti-Asthmatics-Bronchodilators

[0084] A. Isoproterenol Hydrochloride as polar lingual spray Amounts preferred amount most preferred amount isoproterenol 0.1-10  0.2-7.5 0.5-6   Hydrochloride water  5-90 10-80 50-75 ethanol  1-80  3-50  5-10 polyethylene  1-80  3-50  5-15 glycol Sorbitol 0.1-5   0.2-4   0.4-1.0 aspartame 0.01-0.5  0.02-0.4  0.04-0.1  flavors 0.1-5   1-4 2-3

[0085] B. Terbutaline sulfate as polar lingual spray Amounts preferred amount most preferred amount terbutaline sulfate 0.1-10  0.2-7.5 0.5-6   water  5-90 10-80 50-75 ethanol  1-10 2-8 2.5-5   Sorbitol 0.1-5   0.2-4   0.4-1.0 aspartame 0.01-0.5  0.02-0.4  0.04-0.1  flavors 0.1-5   1-4 2-3

[0086] C. Terbutaline as non-polar lingual spray Amounts preferred amount most preferred amount terbutaline 0.1-10  0.2-7.5 0.5-6   migylol 25-50 30-45 35-40 isobutane  5-60 10-50 20-35 polyoxyethylated 25-50 30-45 35-40 oleic glycerides flavors 0.1-10  1-8   5-7.5

[0087] D. Theophylline polar bite capsule Amounts preferred amount most preferred amount theophylline  5-50 10-40 15-30 polyethylene 20-60 25-50 30-40 glycol glycerin 25-50 35-45 30-40 propylene glycol 25-50 35-45 30-40 flavors 0.1-5   1-4 2-3

[0088] E. Albuterol sulfate as polar lingual spray preferred most preferred Amounts amount amount albuterol sulfate 0.1-10   0.2-7.5 0.5-6 water   5-90   10-80   50-75 ethanol   1-10   2-8 2.5-5 Sorbitol 0.1-5  0.2-4   0.4-1.0 aspartame  0.01-0.5   0.02-0.4  0.04-0.1 flavors 0.1-5    1-4   2-3

Example 12

[0089] Polar Solvent Formulations Using a Propellant: A. Sulfonylurea Preferred Most-Preferred Amount Amount Amount glyburide 0.1-25% 0.5-15%  0.6-10% Ethanol  40-99%  60-97%   70-97% Water 0.01-5% 0.1-4%  0.2-2% Flavors 0.05-10%  0.1-5% 0.1-2.5%  Propellant   2-10%   3-5%   3-4%

[0090] B. Prostaglandin E (vasodilator) Preferred Most-Preferred Amount Amount Amount prostaglandin E₁ 0.01-10% 0.1-5% 0.2-3% Ethanol   10-90%  20-75%   25-50%  Propylene glycol   1-90%  5-80%  10-75%  Water  0.01-5% 0.1-4% 0.2-2% Flavors 0.05-10% 0.1-5% 0.1-2.5%   Propellant   2-10%   3-5%   3-4%

[0091] C. Promethazine (antiemetic, sleep inducer, and CNS active amine) Preferred Most-Preferred Amount Amount Amount promethazine 1-25% 3-15%  5-12% Ethanol 10-90%  20-75%  25-50% Propylene glycol 1-90% 5-80% 10-75% Water 0.01-5%   0.1-4%   0.2-2%  Flavors 0.05-10%   0.1-5%  0.1-2.5%   Propellant 2-10%  3-5%  3-4%

[0092] D. Meclizine Preferred Most-Preferred Amount Amount Amount meclizine 1-25% 3-15% 5-12%  Ethanol 1-15% 2-10% 3-6 Propylene glycol 20-98%  5-90% 10-85%  Water 0.01-5%   0.1-4%  0.2-2%   Flavors 0.05-10%   0.1-5%  0.1-2.5%    Propellant 2-10%  3-5% 3-4% 

What is claimed is:
 1. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount of between 0.001 and 60 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and a polar solvent in an amount between 30 and 99 percent by weight of the total composition.
 2. The composition of claim 1, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.
 3. The composition of claim 2, wherein the polar solvent is present in an amount between 37 and 98 percent by weight of the total composition, the active compound is present in an amount between 0.005 and 55 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.5 and 8 percent by weight of the total composition.
 4. The composition of claim 3, wherein the polar solvent is present in an amount between 60 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.01 and 40 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.75 and 7.5 percent by weight of the total composition.
 5. The composition of claim 1, wherein the polar solvent is selected from the group consisting of polyethylene glycols having a molecular weight between 400 and 1000, C₂ to C₈ mono- and poly-alcohols, and C₇ to C₁₈ alcohols of linear or branched configuration.
 6. The composition of claim 1, wherein the polar solvent comprises aqueous polyethylene glycol.
 7. The composition of claim 1, wherein the polar solvent comprises aqueous ethanol.
 8. The composition of claim 1, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
 9. The composition of claim 1, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
 10. The composition of claim 1, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
 11. The composition of claim 1, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
 12. The composition of claim 2, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
 13. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim
 1. 14. The method of claim 13, wherein the amount of the spray is predetermined.
 15. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount of between 0.1 and 25 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; a polar solvent in an amount between 10 and 97 percent by weight of the total composition; and a propellant in an amount between 2 and 10 percent by weight of the total composition, wherein said propellant is a C₃ to C₈ hydrocarbon of linear or branched configuration.
 16. The composition of claim 15, further comprising a flavoring agent in an amount between 0.05 and 10 percent by weight of the total composition.
 17. The composition of claim 16, wherein the polar solvent is present in an amount between 20 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.1 and 15 percent by weight of the total composition, the propellant is present in an amount between 2 and 5 percent by weight of the composition, and the flavoring agent is present in an amount between 0.1 and 5 percent by weight of the total composition.
 18. The composition of claim 17, wherein the polar solvent is present in an amount between 25 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.2 and 25 percent by weight of the total composition, the propellant is present in an amount between 2 and 4 percent by weight of the composition, and flavoring agent is present in an amount between 0.1 and 2.5 percent by weight of the total composition.
 19. The composition of claim 15, wherein the polar solvent is selected from the group consisting of polyethyleneglycols having a molecular weight between 400 and 1000, C₂ to C₈ mono- and poly-alcohols, and C₇ to C₁₈ alcohols of linear or branched configuration.
 20. The composition of claim 19, wherein the polar solvent comprises aqueous polyethylene glycol.
 21. The composition of claim 19, wherein the polar solvent comprises aqueous ethanol.
 22. The composition of claim 15, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
 23. The composition of claim 15, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
 24. The composition of claim 15, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
 25. The composition of claim 15, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
 26. The composition of claim 16, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
 27. The composition of claim 15, wherein the propellant is selected from the group consisting of propane, N-butane, iso-butane, N-pentane, iso-pentane, neo-pentane, and mixtures thereof.
 28. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim
 15. 29. The method of claim 28, wherein the amount of the spray is predetermined.
 30. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount between 0.005 and 55 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and a non-polar solvent in an amount between 30 and 99 percent by weight of the total composition.
 31. The composition of claim 30, further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition.
 32. The composition of claim 30, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
 33. The composition of claim 30, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
 34. The composition of claim 30, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxyniorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
 35. The composition of claim 30, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
 36. The composition of claim 31, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
 37. The composition of claim 30, wherein the solvent is selected from the group consisting of (C₂-C₂₄) fatty acid (C₂-C₆) esters, C₇-C₁₈ hydrocarbons of linear or branched configuration, C₂-C₆ alkanoyl esters, and triglycerides of C₂-C₆ carboxylic acids.
 38. The composition of claim 37, wherein the solvent is miglyol.
 39. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim
 30. 40. The method of claim 39, wherein the amount of the spray is predetermined.
 41. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount between 0.05 and 50 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and a non-polar solvent in an amount between 19 and 85 percent by weight of the total composition; and a propellant in an amount between 5 and 80 percent by weight of the total composition, wherein said propellant is a C₃ to C₈ hydrocarbon of linear or brancehed configuration.
 42. The composition of claim 41, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.
 43. The composition of claim 42, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
 44. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount between 0.01 and 40 percent by weight of the total composition selected from the group consisting of anti-opioid agents, anti-migraine agents, pain control agents, anesthetics, and mixtures thereof; and a non-polar solvent in an amount between 25 and 89 percent by weight of the total composition; a propellant in an amount between 10 and 70 percent by weight of the total composition, wherein said propellant is a C₃ to C₈ hydrocarbon of linear or brancehed configuration; and A flavoring agent is present in an amount between 1 and 8 percent by weight of the total composition.
 45. The composition of claim 44, wherein the propellant is present in an amount between 20 and 70 percent by weight of the total composition, the non-polar solvent is present in an amount between 25 and 75 percent by weight of the total composition, the active compound is present in an amount from between 0.25 and 35 percent by weight of the total composition, and the flavoring agent is present in an amount between 2 and 7.5 percent by weight of the total composition.
 46. The composition of claim 42, wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pantane, iso-pentane, neo-pentane, and mixtures thereof.
 47. The composition of claim 46, wherein the propellant is n-butane or iso-butane and has a water content of not more than 0.2 percent and a concentration of oxidizing agents, reducing agents, Lewis acids, and Lewis bases of less than 0.1 percent.
 48. The composition of claim 41, wherein the solvent is selected from the group consisting of (C₂-C₂₄) fatty acid (C₂-C₆) esters, C₇-C₁₈ hydrocarbons of linear or branched configuration, C₂-C₆ alkanoyl esters, and triglycerides of C₂-C₆ carboxylic acids.
 49. The composition of claim 48, wherein the solvent is miglyol.
 50. The composition of claim 41, wherein the active compound is an anti-opioid agent selected from the group consisting of naloxone, nalmefene, naltrexone, cholecystokinin, nociceptin, neuropeptide FF, oxytocin, vasopressin, and mixtures thereof.
 51. The composition of claim 41, wherein the active compound is an anti-migraine agent selected from the group consisting of frovatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, naratriptan, almotriptan, ergotamine, diethylergotamine, sumatriptan, and mixtures thereof.
 52. The composition of claim 41, wherein the active compound is a pain control agent selected from the group consisting of non-steroidal anti-inflammatory drugs, alfentanil, butorphanol, codeine, dezocine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, propoxyphene, pentazocine, sufentanil, tramadol, and mixtures thereof.
 53. The composition of claim 41, wherein the active compound is an anesthetic selected from the group consisting of benzonatate, bupivacaine, desflurane, enflurane, isoflurane, levobupivacaine, lidocaine, mepivacaine, prilocalne, propofol, rapacuronium bromide, ropivacaine, sevoflurane, ketamine, and mixtures thereof.
 54. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim
 41. 55. The method of claim 54, wherein the amount of the spray is predetermined. 